Drug combination reduces colon cancer risk: study (Reuters - 14/04/2008)

Combining a low dose of targeted cancer-fighter DFMO with an anti-inflammatory drug reduces the risk of new colorectal polyps, an early sign of colon cancer, by as much as 95 percent, researchers said on Monday. A study conducted by the University of California, Irvine, also found that the drug combination is much less toxic than chemotherapy. "There is a great hope that we will be able to prevent colon cancer effectively using this method. We had not been able to do this before due to the high toxicity of available therapies," said Dr. Frank Meyskens, director of the university's cancer center.
He lead a study in which 375 patients with at least one previous colorectal polyp, also known as adenomas, were treated with either a combination of DFMO (difluoromethylornithine) and sulindac, a non-steroidal anti-inflammatory drug, or placebo. The results were so encouraging that the study was stopped early. After three years, the overall risk of recurrent adenoma was 12.3 percent in treated patients, compared with 41.1 percent for patients in the placebo group, or a 70 percent risk reduction.For patients with more than one previous polyp, 0.7 percent of treated patients had a recurrence, compared with 13.2 percent of placebo patients -- a 95 percent reduction.

The researchers said an analysis of side effects and toxicity found no difference between the treatment and placebo groups. There also was no difference in side effects requiring overnight hospitalization, gastrointestinal side effects or cardiovascular side effects between the two groups. DFMO is the basis of the drug eflornithine, which was initially developed as a cancer medication, but is now used to treat African sleeping sickness. A cream formulation of eflornithine is marketed as a hair removal agent under the brand name Vaniqa.Sulindac is sold by Merck & Co Ltd under the brand name Clinoril as a treatment for arthritis and other inflammatory conditions. Meyskens said larger trials will be needed to assess the risk of cardiovascular and other adverse side effects, as well as to determine whether the incidence of actual colorectal cancer can be reduced in either patients with low stage prior colorectal cancers or in very high risk individuals.Chronic use of other NSAID's, such as Merck's Vioxx, has been linked to an increased risk of 
heart attack and stroke.

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Bowel cancer screening halves emergency admissions, cuts deaths- (ANI- 2/12/2007)

A pilot site has revealed that bowel cancer screening halves emergency admissions for the disease and significantly cuts death rates. The figures refer to tests carried out in Coventry and Warwickshire in the Midlands. In the study, the feasibility of bowel cancer was screened for those aged 50 to 69 years, using postal tests that picked up hidden traces of blood in the stool (faecal occult blood tests).Blood in the stool is a cardinal sign of cancerous and pre-cancerous changes in the bowel.

The research team tracked the number of emergency admissions for, and deaths within 30 days from, bowel. The timeframe spanned from 1999, a year before the pilot began, to 2004, when the programme had been running for five years. During the entire period, 1236 new cases of bowel cancer were diagnosed, equating to 200 cases a year.

In 1999, just under 30 percent of bowel cancer patients had to be admitted as an emergency. By 2004, this figure had fallen to just under 16percent. As a result, the number of emergency operations required halved, and the number of patients dying within 30 days also fell. In 1999 almost half of those undergoing emergency surgery died. By 2004, this figure had fallen to just 13 percent. The number of Dukes C or stage 3 relatively advanced bowel cancers also fell from 38 in 1999 to 16 in 2004, although the proportion of these cases requiring emergency care remained the same.

The researchers of the study conclude that bowel cancer screening is effective, yet take-up of the test among those who are eligible appears to be falling. They said that it is important that patients and their family doctors are aware of the benefits of screening. The findings will be published in the journal Gut. 

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Genes May Explain Role of Race in Colon Cancer Risk- (HealthDay- 28/11/2007) 

Genes may contribute to disparities in colorectal cancer rates between ethnic and racial groups, a new U.S. review suggests. The research team, led by investigators at the University of Pittsburgh, analyzed 26 studies that included more than 25,000 people. They found that people who have two "T" copies of the MTHFR gene that metabolizes folate -- a chemical needed to produce and maintain new cells -- are 19 percent less likely to develop colorectal cancer than people with two "C" copies of the gene.

When they looked at specific racial/ethnic groups, the reviewers found that the risk of colorectal cancer in people with the two "T" copies, compared to those with the two "C" copies, was 31 percent less in Asians, 8 percent less in whites, and 4 percent less in black Americans. They also found that Hispanics who had one "T" copy and one "C" copy of the gene were 20 percent more likely to develop colorectal cancer than Hispanics with two "C" copies of the gene. However, the researchers said this finding was not statistically significant. The results of the analysis were to be presented Wednesday at the American Association for Cancer Research's conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, in Atlanta.

The study shows that two copies of the "T" version of the gene "may be protective in different degrees against colorectal cancer in some populations but not in others," lead investigator Mary A. Garza, deputy director of the Center for Minority Health in the University of Pittsburgh's Graduate School of Public Health, said in a prepared statement. The finding that two "T" copies of the MTHFR gene may help protect against colorectal cancer in certain racial/ethnic groups warrants further study, she said. This is the first pooled analysis to examine the association between specific genes and the risk of developing colorectal cancer in racial/ethnic groups, according to Garza.

"We are trying to unlock the role genetics, through gene-environment interactions, may play in understanding the underlying causes of health disparities," she said. Overall, colorectal cancer death rates in the United States have been declining, but blacks and other minorities account for a disproportionate share of colorectal cancer patients. "This disparity exists even after accounting for various environmental and social factors, so it makes sense that genetics could play a contributing role in this cancer disparity," Garza said.

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Transition from polyp to cancer age-dependent-(Reuters- 22/11/2007) 

Men and women with advanced colorectal polyps have a similar risk of progressing to colorectal cancer (CRC) and the risk increases with age in both sexes, according to a study conducted in Germany. Colorectal polyps (also called adenomas) are found in up to 40 percent of adults over 50. Fewer than 5 percent of them turn cancerous. To come up with age- and sex-specific estimates of transition rates from advanced polyps to CRC, Dr. Hermann Brenner from the German Cancer Research Center, Heidelberg and colleagues used combined data from 840,149 screening colonoscopies and from national population-based cancer registries.

They report in the journal Gut that annual transition rates increase from 2.6 percent in women aged 55 to 59 years to 5.6 percent in women aged 80 and older. For men in these age groups, transition rates increase from 2.6 percent to 5.1 percent. In their analyses, estimates of 10-year cumulative risk increased from 25.4 percent at age 55 years to 42.9 percent at age 80 years in women, with corresponding increases from 25.2 percent to 39.7 percent in men."Our finding that advanced adenoma transition rates are strongly age-dependent could have important clinical implications, possibly including a higher age at first screening or differential endoscopy intervals according to age," Brenner and colleagues write. "However, additional risk factors, such as family history of CRC, also have to be taken into account," they note.

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Drug Helps Fight Late-Stage Colon Cancer in Some Patients- (HealthDay- 14/11/2007)

A highly targeted biologic drug called cetuximab (Erbitux) is the first to extend the survival of patients with advanced colon cancer who have otherwise proved resistant to conventional chemotherapy, Canadian researchers confirmed. But the drug, which costs $12,000 a month in the United States, appears to be effective in only about one-third of colon tumors, based on their specific gene profile, experts added.

"That's a significant number, but it still leaves a large proportion [of patients] who aren't benefiting," noted lead researcher Dr. Derek Jonker, assistant professor of medicine at the University of Ottawa and a medical oncologist at the Ottawa Hospital. Nevertheless, the success of any new drug is welcome, he added. "Until now, no anticancer therapy had demonstrated an improvement in survival in patients for whom chemotherapy was no longer effective, and for whom supportive care was the only available treatment," Jonker said. "So, cetuximab provides new hope for these patients."

The findings were reported in the Nov. 15 issue of the New England Journal of Medicine. The study was funded by the National Cancer Institute of Canada, as well as ImClone Systems and Bristol-Myers Squibb, the two companies that developed the drug. Colorectal cancer is the third most common kind of cancer and the third leading cause of cancer death in the United States. As Jonker explained, most patients are treated with either surgery or conventional chemotherapy, which typically targets cellular DNA.

Unfortunately, almost all patients with advanced or metastasized colon cancer will develop resistance to standard chemotherapy drugs, he said. "However, now we have a new class of drugs known as the biologically targeted therapies, such as cetuximab, and these drugs are targeted to different aspects of the tumor biology," Jonker explained. "Many of them are targeted at receptors or signals that trigger a cancer cell to grow."

In the case of cetuximab, the drug's target is the epidermal growth factor receptor (EGFR), which is found in especially high concentrations on colon cancer cells. Because biologic drugs are finely targeted to affect cancer cells and not healthy cells, they typically have fewer side effects than standard chemotherapy. In 2004, the U.S. Food and Drug Administration granted cetuximab conditional approval for use in patients with late-stage, chemotherapy-resistant colon cancer. At the time, the agency stated that full approval hinged on the outcome of the Canadian trial.

In October, and based on the new findings, the agency followed through and gave the drug its full approval for this new indication. In the trial, Jonker's team administered individualized doses of cetuximab to 287 colon cancer patients treated between late 2003 and August 2005. All of the patients had proven resistant to standard chemotherapy. Another 285 patients received supportive/palliative care only -- the usual option for patients in this situation.

Compared to those who didn't receive the drug, overall survival for patients receiving cetuximab improved by 23 percent, while survival without any sign of disease progression rose by 32 percent, the research team reported. The incidence of side effects -- including skin rash -- was 78.5 percent in the cetuximab group versus about 59 percent for the control group. One key point, however, was that increases in survival were found only among the 31.4 percent of patients who actually responded to cetuximab, meaning that their cancer stopped growing.

That's probably due to the fact that cetuximab (as well as a related drug, panitumumab) only works against a specific subtype of colon cancer cell -- those carrying an unmutated version of a particular gene called KRAS. "Mutated KRAS almost guarantees no benefit" from cetuximab, said one expert, Dr. Axel Grothey, a professor of oncology and chairman of the colorectal cancer group at the Mayo Clinic, in Rochester, Minn.

For that reason, he said, pre-treatment gene testing may prove crucial to decisions as to whether a particular patient receives cetuximab or not. Because it is so expensive -- the costliest drug used today against colon cancer -- and because it can induce side effects, "I would like cetuximab to be used in a more individualized way," Grothey said. He said that most cancer centers, including the Mayo Clinic, do not yet have technologies in place to test tumors for KRAS, but many are looking into it.

Jonker agreed that, ideally, KRAS testing and the use of cetuximab would go hand-in-hand. That way, he said, "We wouldn't have to put [patients] through treatment, and we wouldn't have to suffer the cost of treatment for people who may not even respond to the drug." Studies are already under way to see if adding cetuximab to other therapies will boost survival even further, Jonker said. "The future of cetuximab is likely to be in combination with chemotherapy or other biologically targeted therapies, where the benefits of cetuximab might be further enhanced," he said. The drug might also work better if given earlier in the disease process, before patients have developed resistance to chemotherapy. In any case, the Canadian trial does give colon cancer patients some new reason for hope, Grothey said. "We need this drug," he said, "and we probably need it even earlier."

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Study Challenges Colon Cancer Surgery Follow-Up (HealthDay- 13/11/2007) 

A new study is questioning the conventional wisdom of checking on the health of 12 lymph nodes after colon cancer surgery. These post-op checks have been thought to be a good indicator of patient survival, but new data is casting that notion in doubt. "What we are finding is that focusing on this quality indicator may not have much positive value for predicting patient outcome," said the study's lead author, Dr. Sandra L. Wong, assistant professor of surgery at the University of Michigan, Ann Arbor.

Wong's team published its report in the Nov. 14 issue of the Journal of the American Medical Association. The routine examination of 12 lymph nodes after colon cancer surgery has been endorsed by the National Quality Forum, a respected organization backed by such prestigious bodies as the American Cancer Society and the American Society of Clinical Oncology. However, the Michigan study of more than 30,000 people who underwent colon cancer surgery provided no support for the protocol. One expert wasn't surprised by the results.

"People have been interpreting information relating the number of nodes examined and survival in a very simplistic way," said Dr. Nancy N. Baxter, assistant professor of surgery at the University of Toronto and co-author of an accompanying editorial. "That relationship is probably pretty complex, due at least in part to the underlying biology of the tumor," she said. Using information from the Medicare-linked National Surveillance and End Results data base, Wong's team divided hospitals where the surgery was done into four groups, based on the proportion of patients who had 12 or more lymph nodes examined. They then assessed patient survival rates for each group of hospitals, adjusting for patient and doctor characteristics.

Hospitals with the highest proportion of patients with 12 or more lymph nodes examined tended to treat lower-risk patients and have a higher volume of surgery. After adjusting for these factors, the researchers found no statistically significant relationship between the number of lymph nodes examined and patients' survival after surgery. The idea of examining lymph nodes to estimate survival does make sense, experts say. That's because death is more likely if the cancer spreads beyond the colon, and the route of spread is typically through the lymph nodes.

However, Wong and her colleagues found that hospitals in the study tended to find the same number of lymph nodes positive for cancer, no matter how many nodes they examined. There are several possible explanations for this seeming paradox, including individual variations in dissection or surgical techniques, Wong said. More studies looking at further clinical details may get an answer, she said.

Meanwhile, Wong said, the findings indicated a need to reconsider the 12-node rule, because there is a limit to the resources that can be expended per patient, she said. "If we spend a lot of resources to exact the 12-node exam as the standard of care, we're going to miss the opportunity to improve in other ways," she said. It would be a mistake to focus entirely on this one indicator of quality, she said. "Further studies are important, but what we need are better quality indicators," Wong said. She said she had no immediate suggestions about the sort of characteristics that should be examined, except that "we need to look at broader indicators."

For her part, Baxter said that perhaps too much emphasis was being placed on node numbers and diagnoses. "I don't think setting benchmarks for the number of nodes to be examined will change the outcome for a substantial number of patients," she said. "We should concentrate on things we know will help. For example, we know that many patients with stage 3 colon cancer don't get chemotherapy." Stage 3 cancer has spread to the lymph nodes but not beyond them. "There is a lot of work to be done in terms of getting treatment we know helps patients, to patients," Baxter said. But the relationship between the number of nodes examined and patient survival should continue to be explored, Baxter said. "There may be some underlying biological factor we could use," she added.

Another expert also said more research needs to be done. "In many ways, this study confirms a lot of prior findings about lymph nodes and survival," said Dr George Chang, assistant professor of surgical oncology at the University of Texas M. D. Anderson Cancer Center in Houston. "But it highlights the complexity of that relationship." Even in the quarter of hospitals in which the largest number of lymph nodes were examined, "only 61 percent of patients had 12 looked at," Chang said. "Perhaps examination of a considerably larger number is required to predict survival."

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New versions of curry ingredient to fight cancer (Reuters- 6/11/2007)

Scientists in Japan have created two synthetic versions of an ingredient in curry that is noted for its potential to fight cancer. Some studies have suggested that curcumin, the yellowish component in turmeric that gives curry its flavor, can suppress tumors and that people who eat lots of curry may be less prone to the disease. However, curcumin loses its anti-cancer attributes quickly when ingested.

The scientists wrote in the latest issue of Molecular Cancer Therapeutics that they had synthesized two variations -- GO-Y030 and GO-Y031 -- which have proved more potent and lasting than natural curcumin. They tested them in mice with colorectal cancer and found that they worked far better. "Our new analogues (synthetic versions) have enhanced growth suppressive abilities against colorectal cancer cell lines, up to 30 times greater than natural curcumin," said Hiroyuki Shibata, associate professor at Tohoku University's Institute of Development, Ageing and Cancer.

"In a mouse model for colorectal cancer, mice fed with five milligrams of GO-Y030 or GO-Y031 fared 42 and 51 percent better, respectively, than did mice in the control group." Like curcumin, the two synthetic versions may be able to fight other cancers, such as gastric cancer and cancer of the breast, pancreas and lung, they added.

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More power to turmeric in its fight against cancer (IANS- 5/11/2007)

That turmeric, a key flavour in Indian curry, has anti-cancer properties is well known. But now scientists have improved upon the condiment, making it more potent against the killer disease. Researchers at Tohoku University in Sendai, Japan, have identified and synthesized two molecular analogues in curcumin - the yellowish component in turmeric that gives curry its flavour - that are up to 30 times as potent as natural curcumin. Findings of the study were presented at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine here Sunday. 

According to lead researcher Hiroyuki Shibata, curcumin is known to suppress genes that promote cell growth as well as kill cancerous cells. But unfortunately, adds Shibata, natural curcumin has 'low bioavailability' - that is, it quickly loses its anti-cancer attributes when ingested. So, to enhance the therapeutic potential of curcumin, Shibata and his colleagues synthesized and tested 90 variations of the molecule's structure - and two proved to be more potent and bioavailable than natural curcumin. 

Mice fed on these two molecular analogues fared up to 51 percent better than did mice in a control group. In 2006, the researchers published structural data for the two molecules - named GO-Y030 and GO-Y031 - in the journal Molecular Cancer Therapeutics, and they continue to study the mechanisms behind the molecules' apparent potencies. 

In its natural form, the curcumin molecule is composed of two ring structures linked by a chain of seven carbon atoms. The active ring structures of GO-Y030 and GO-Y031 are, however, linked by a shorter, five-carbon chain, which, Shibata says, might account for their enhanced potency. Like curcumin, the researchers believe the new analogues have clinical potential that extends beyond colorectal cancer. 'In addition to colorectal cancer, the a catenin-degrading abilities of these molecules could apply to other forms of cancer, such as gastric cancer,' said Shibata. 

New test for inherited bowel cancer-(Yahoo News- 17/10/2007)

A laboratory test can detect hereditary bowel cancer twice as effectively as older methods and could save many lives, Australian researchers say. Dubbed the "Melbourne criteria" in the Journal of Clinical Oncology, the test would particularly benefit the relatives of early onset bowel cancer patients. The pathology test screened surgically-removed bowel tumours for proteins normally expressed by four genes linked to bowel cancer. Faults in the genes, known as mismatch repair genes, have previously been found in bowel cancer patients, especially those with disease at a young age.

University of Melbourne epidemiologist John Hopper said an absence of specific proteins in tumours was an indication of whether the cancer was associated with an inherited fault, even if the patient had no family history of bowel cancer. The university's pathology laboratory, led by scientist Melissa Southey, studied the tumours of 105 Melbourne bowel cancer patients under the age of 45, irrespective of family history. They found 18 patients - or 17 per cent - were carriers of a mutation in one of the four suspect genes.

"Individuals with a faulty mismatch repair gene are at high risk of developing bowel cancer as well as some other cancers," Professor Hopper said in an interview. "On average, half their close relatives will have inherited the same genetic fault." Therefore, those most likely to gain from the testing are family members of bowel cancer patients found to share the genetic fault but who are yet to develop the disease. "With bowel cancer, we know that good clinical management and surveillance can save lives," Prof Hopper said.

Once the test showed a patient's cancer was possibly inherited, more expensive DNA screening was required to pinpoint the genetic fault, he said. Prof Hopper said around half of the high-risk families identified in the Melbourne study would have been missed if family history was relied upon alone.
"Using the new Melbourne criteria, none would be missed, and the genetic fault would have been found in 60 to 70 per cent of the patients identified as likely to have inherited the cancer," Prof Hopper said. He has called for the procedure to be taken up by bowel cancer specialists and hospital pathology laboratories Australia-wide.

"I don't think we're going to necessarily eradicate this disease but we're certainly going to be able to make a big cut in its impact by using this new procedure," he said. "The most important thing about these genes is that the people with a genetic risk are getting their cancers at a young age, before they turn 50. "It's killing people in the prime of their life." Prof Hopper said the tumour test was covered by Medicare.

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Long-Term Aspirin Use Cuts Colorectal Cancer Risk, But ... (HealthDay News-23/08/2005)

People who take aspirin or a non-steroidal anti-inflammatory drug (NSAID) such as Advil or Motrin to treat their arthritis or other pain may also be lowering their risk of colorectal cancer. But the benefits of the drug therapy don't become significantly apparent for at least a decade, according to new research. And the therapy poses considerable health risks, including gastrointestinal bleeding as a result of such long-term use. Harvard researchers report that long-term use of aspirin or NSAIDs cuts colorectal risk by as much as 53 percent. The risk reduction depended on the dose taken weekly and the number of years taken, according to the study, published in the Aug. 24-31 issue of the Journal of the American Medical Association.

"Regular long-term use of aspirin did reduce the risk of colorectal cancer," said the study's lead author, Dr. Andrew Chan, an instructor of medicine at Harvard Medical School and a staff physician at Massachusetts General Hospital in Boston. However, Chan also urged caution, because long-term use of these medications can cause serious side effects, including gastrointestinal bleeding. He said the researchers were not recommending either aspirin or NSAIDs for routine colorectal cancer prevention. "You have to weigh both the risks of colorectal cancer and the side effects of using these drugs. There are other prevention strategies, like colorectal cancer screening, and we need to examine what the benefit of aspirin would be above and beyond current prevention," said Chan. The American Cancer Society agreed. In a statement, Eric Jacobs, a senior epidemiologist for the society, said that "use of aspirin at any dose to prevent cancer is not recommended by the American Cancer Society or any other group because of the potential for serious side effects."


Although advances have been made in screening and detection of colorectal cancer, it still remains the second most deadly form of the disease, after lung cancer. Each year, about 56,000 Americans die from colorectal cancer and 145,000 people will be newly diagnosed with the illness, according to the American Cancer Society. Using information from the prospective Nurses' Health Study, the researchers examined data on nearly 83,000 women who had been providing information on their medication use at least every two years. The women were between 30 and 55 at the start of the study. In this group, 962 women developed colorectal cancer during the 20-year study period.

Women who regularly used aspirin were at a 23 percent reduced risk of colorectal cancer compared to non-regular aspirin users, according to the study. Significant risk reduction didn't appear until after a decade of use, however. The researchers also found that the more aspirin the women took, the lower their colorectal cancer risk. Women who took two to five standard aspirin tablets weekly had an 11 percent reduced risk compared to non-users. The risk fell by 22 percent among women who took six to 14 tablets weekly, while women taking more than 14 aspirin tablets a week had a 32 percent decrease in their risk of colorectal cancer. Women who took more than 14 tablets weekly for more than 10 years had the greatest risk reduction, 53 percent, according to the researchers. However, Chan said that women on the highest doses of aspirin also increased their risk of gastrointestinal bleeding by 57 percent.


Dose also mattered for NSAIDs -- drugs that include Advil, Aleve and Motrin. Women taking two to five tablets a week lowered their colorectal cancer risk by 9 percent, while those taking six to 14 tablets weekly had a 31 percent decreased risk. Women taking more than 14 NSAID doses a week reduced their risk by 46 percent, according to the study. NSAIDs were also associated with an increased risk of gastrointestinal bleeding, Chan said. Chan said the researchers also looked at the effects of acetaminophen (Tylenol) and weren't surprised when they found no benefit. That's because the researchers suspect that inhibition of the enzyme cox 2 -- something both aspirin and NSAIDs do -- may be what's reducing colorectal cancer risk. Acetaminophen does not inhibit cox 2.

Two prescription cox 2 inhibitor NSAIDS, Vioxx and Bextra, have been pulled from the market because long-term use has been linked to serious cardiovascular side effects, but one such drug, Celebrex, remains on drugstore shelves. Chan said his team's study was unable to determine whether long-term use of over-the-counter NSAIDs might have similar effects. While the researchers aren't recommending the routine use of aspirin or NSAIDs for colorectal cancer prevention, Chan said there may be a use for these drugs in some patients, perhaps those at an especially high risk for the malignancy. But, he said, it's too soon to know for sure. What this study does do, he said, is "validate our understanding of the mechanism behind colorectal cancer and opens further avenues of research." Both Chan and Jacobs said the best way to prevent colorectal cancer is to undergo regular colorectal cancer screenings beginning at age 50, or even sooner for individuals at high risk for the disease.

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